Structure and plasticity of Endophilin and Sorting Nexin 9.
Endophilin and Sorting Nexin 9 (Snx9) play key roles in endocytosis by membrane curvature sensing and remodeling via their Bin/Amphiphysin/Rvs (BAR) domains. BAR and the related F-BAR domains form dimeric, crescent-shaped units that occur N- or C-terminally to other lipid-binding, adaptor, or catalytic modules. In crystal structures, the PX-BAR unit of Snx9 (Snx9(PX-BAR)) adopts an overall compact, moderately curved conformation. SAXS-based solution studies revealed an alternative, more curved state of Snx9(PX-BAR) in which the PX domains are flexibly connected to the BAR domains, providing a model for how Snx9 exhibits lipid-dependent curvature preferences. In contrast, Endophilin appears to be rigid in solution, and the SH3 domains are located at the distal tips of a BAR domain dimer with fixed curvature. We also observed tip-to-tip interactions between the BAR domains in a trigonal crystal form of Snx9(PX-BAR) reminiscent of functionally important interactions described for F-BAR domains.
Wang
Qi
Q
Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Kaan
Hung Yi Kristal
HY
Hooda
Reshma Noordin
RN
Goh
Shih Lin
SL
Sondermann
Holger
H
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D018360:Crystallography, X-Ray; D006801:Humans; D007700:Kinetics; D051379:Mice; D008954:Models, Biological; D008958:Models, Molecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D053838:Scattering, Small Angle; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D014961:X-Ray Diffraction
D048868:Adaptor Proteins, Signal Transducing; C400533:SNX9 protein, human; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins; C504641:endophilin A1 protein, mouse